Intermittent access to 20% ethanol induces high ethanol consumption in Long-Evans and Wistar rats

BACKGROUND: There has been some difficulty getting standard laboratory rats to voluntarily consume large amounts of ethanol without the use of initiation procedures. It has previously been shown that standard laboratory rats will voluntarily consume high levels of ethanol if given intermittent-access to 20% ethanol in a 2-bottle-choice setting [Wise, Psychopharmacologia 29 (1973), 203]. In this study, we have further characterized this drinking model. METHODS: Ethanol-naïve Long-Evans rats were given intermittent-access to 20% ethanol (three 24-hour sessions per week). No sucrose fading was needed and water was always available ad libitum. Ethanol consumption, preference, and long-term drinking behaviors were investigated. Furthermore, to pharmacologically validate the intermittent-access 20% ethanol drinking paradigm, the efficacy of acamprosate and naltrexone in decreasing ethanol consumption were compared with those of groups given continuous-access to 10 or 20% ethanol, respectively. Additionally, ethanol consumption was investigated in Wistar and out-bred alcohol preferring (P) rats following intermittent-access to 20% ethanol. RESULTS: The intermittent-access 20% ethanol 2-bottle-choice drinking paradigm led standard laboratory rats to escalate their ethanol intake over the first 5 to 6 drinking sessions, reaching stable baseline consumption of high amounts of ethanol (Long-Evans: 5.1 +/- 0.6; Wistar: 5.8 +/- 0.8 g/kg/24 h, respectively). Furthermore, the cycles of excessive drinking and abstinence led to an increase in ethanol preference and increased efficacy of both acamprosate and naltrexone in Long-Evans rats. P-rats initiate drinking at a higher level than both Long-Evans and Wistar rats using the intermittent-access 20% ethanol paradigm and showed a trend toward a further escalation in ethanol intake over time (mean ethanol intake: 6.3 +/- 0.8 g/kg/24 h). CONCLUSION: Standard laboratory rats will voluntarily consume ethanol using the intermittent-access 20% ethanol drinking paradigm without the use of any initiation procedures. This model promises to be a valuable tool in the alcohol research field.

Dynamic axial ligand-site exchange in facially discriminated ruthenium(II) carbonyl and rhodium(III) halide metalloporphyrins

For a series of six-coordinate Ru(II)(CO)L or Rh(III)(X–)L porphyrins which are facially differentiated by having a naphthoquinol- or hydroquinol-containing strap across one face, we show that ligand migration from one face to the other can occur under mild conditions, and that ligand site preference is dependent on the nature of L and X–. For bulky nitrogen-based ligands, the strap can be displaced sideways to accommodate the ligand on the same side as the strap. For the ligand pyrazine, we show 1 H NMR evidence for monodentate and bidentate binding modes on both faces, dependent on ligand concentration and metalloporphyrin structure, and that inter-facial migration is rapid under normal conditions. For monodentate substituted pyridine ligands there is a site dependence on structure, and we show clear evidence of dynamic ligand migration through a series of ligand exchange reactions.

Is there an App for that? : social media uses for road safety

The use of social media has increased dramatically in recent years in the areas of public health and injury prevention, with many organisations creating online and social media content. Despite the adoption of such media by modern society, research relating to the design and evaluation of social media for the promotion of health issues is very much in its infancy. A timely review of the available evidence in relation to the use of social media campaigns from both the road safety and broader public health context will be undertaken. In particular, this paper will address the questions of what social media should be developed, how it should be evaluated, as well as what should be the key measures of success and to what extent do these measures relate to practically significant outcomes, such as behaviour change. Much like more traditional media campaigns, social media may be best regarded as another approach within the array of potential approaches that a health advertising researcher or practitioner may utilise. With younger demographics becoming less likely to engage with more traditional advertising mediums relative to their preference for social media, social media‟s most important role in the road safety advertising context may be to offer the means of delivering road safety messages to high risk, younger road users.

Gender equity in the professoriate : a cohort study of new women professors in Australia

According to statistics and trend data, women continue to be substantially under- represented in the Australian professoriate, and growth in their representation has been slow despite the plethora of equity programs. While not disputing these facts, we propose that examining gender equity by cohort provides a complementary perspective on the status of gender equity in the professoriate. Based on over 500 survey responses, we detected substantial similarities between women and men who were appointed as professors or associate professors between 2005 and 2008. There were similar proportions of women and men appointed via external or internal processes or by invitation. Additionally, similar proportions of women and men professors expressed a marked preference for research over teaching. Furthermore, there were similar distributions between the genders in the age of appointment to the professoriate. However, a notable gender difference was that women were appointed to the professoriate on average 1.9 years later than mens. This later appointment provides one reason for the lower representation of women compared to men in the professoriate. It also raises questions of the typical length of time that women and men remain in the (paid) professoriate and reasons why they might leave it. A further similarity between women and men in this cohort was their identification of motivation and circumstances as key factors in their career orientation. However, substantially more women identified motivation than circumstances and the situation was reversed for men. The open-ended survey responses also provided confirmation that affirmative action initiatives make a difference to women’s careers.

Quality delivery of mobile video : in-depth understanding of user requirements

The increase of powerful mobile devices has accelerated the demand for mobile videos. Previous studies in mobile video have focused on understanding of mobile video usage, improvement of video quality, and user interface design in video browsing. However, research focusing on a deep understanding of users’ needs for a pleasing quality delivery of mobile video is lacking. In particular, what quality-delivery mode users prefer and what information relevant to video quality they need requires attention. This paper presents a qualitative interview study with 38 participants to gain an insight into three aspects: influencing factors of user-desired video quality, user-preferred quality-delivery modes, and user-required interaction information of mobile video. The results show that user requirements for video quality are related to personal preference, technology background and video viewing experience, and the preferred quality-delivery mode and interactive mode are diverse. These complex user requirements call for flexible and personalised quality delivery and interaction of mobile video.

Detecting gesture force peaks for intuitive interaction

With the release of the Nintendo Wii in 2006, the use of haptic force gestures has become a very popular form of input for interactive entertainment. However, current gesture recognition techniques utilised in Nintendo Wii games fall prey to a lack of control when it comes to recognising simple gestures. This paper presents a simple gesture recognition technique called Peak Testing which gives greater control over gesture interaction. This recognition technique locates force peaks in continuous force data (provided by a gesture device such as the Wiimote) and then cancels any peaks which are not meant for input. Peak Testing is therefore technically able to identify movements in any direction. This paper applies this recognition technique to control virtual instruments and investigates how users respond to this interaction. The technique is then explored as the basis for a robust way to navigate menus with a simple flick of the wrist. We propose that this flick-form of interaction could be a very intuitive way to navigate Nintendo Wii menus instead of the current pointer techniques implemented.

Integration of CENA practice standards for postgraduate emergency nursing assessment

The use of professional competency standards to assess postgraduate nursing student’s clinical performance has been in place since 2004, at the Queensland University of Technology, School of Nursing & Midwifery (SONAM) when the Graduate Certificate in Emergency Nursing degree commenced. Emergency nursing students were assessed in their workplace, using a Clinical Performance Appraisal Tool or CPAT which was based on the Australian College of Critical Care Nurses (ACCCN) Competency Standards. With the subsequent formation of a separate Emergency Nursing Course advisory group in 2007, there was a review of clinical assessment course component. The release of the 2008 CENA revised Practice Standards for the Emergency Nursing Specialist’s, led to the emergency nursing course advisory committee supporting the integration of the CENA practice standards for assessment of emergency nurses in preference to the less relevant ACCCN competency standards. The SONAM emergency nursing study area team commenced the phasing in and progression of the CENA practice standards across the two Graduate Certificate units, and Graduate Diploma and Master of Nursing (emergency) clinical major options in 2009. As some units undertaken in the degree are available to nurses in other disciplines a separate CPAT was devised for the clinical assessments according to speciality context. The team has had to carefully consider how the professional standards are integrated into the teaching and assessment of the unit and not just applied instead of the ACCCN competency standards. Professional standards for the emergency context has also helped tailor course content and learning outcomes to be relevant across a number of emergency nursing contexts in Australia. The assessment of the CPAT is undertaken at the workplace by QUT appointed clinical lecturers. Clinical lecturers need to apply and have suitable postgraduate qualification to undertake the position. The clinical lecturer support role is well established at QUT. The integration of the new CENA practice standards has necessitated a review of the postgraduate assessment of emergency nurses. A clinical lecturer workshop has been organised to review role, scope and how to utilise the new look CENA based CPAT, clinical assessment format.

Saving bitrate vs. pleasing users : where is the break-even point in mobile video quality?

This paper presents a comprehensive study to find the most efficient bitrate requirement to deliver mobile video that optimizes bandwidth, while at the same time maintains good user viewing experience. In the study, forty participants were asked to choose the lowest quality video that would still provide for a comfortable and long-term viewing experience, knowing that higher video quality is more expensive and bandwidth intensive. This paper proposes the lowest pleasing bitrates and corresponding encoding parameters for five different content types: cartoon, movie, music, news and sports. It also explores how the lowest pleasing quality is influenced by content type, image resolution, bitrate, and user gender, prior viewing experience, and preference. In addition, it analyzes the trajectory of users’ progression while selecting the lowest pleasing quality. The findings reveal that the lowest bitrate requirement for a pleasing viewing experience is much higher than that of the lowest acceptable quality. Users’ criteria for the lowest pleasing video quality are related to the video’s content features, as well as its usage purpose and the user’s personal preferences. These findings can provide video providers guidance on what quality they should offer to please mobile users.

Influence of physical and chemical properties of solids on heavy metal adsorption

Partition of heavy metals between particulate and dissolve fraction of stormwater primarily depends on the adsorption characteristics of solids particles. Moreover, the bioavailability of heavy metals is also influenced by the adsorption behaviour of solids. However, due to the lack of fundamental knowledge in relation to the heavy metals adsorption processes of road deposited solids, the effectiveness of stormwater management strategies can be limited. The research study focused on the investigation of the physical and chemical parameters of solids on urban road surfaces and, more specifically, on heavy metal adsorption to solids. Due to the complex nature of heavy metal interaction with solids, a substantial database was generated through a series of field investigations and laboratory experiments. The study sites for the build-up pollutant sample collection were selected from four urbanised suburbs located in a major river catchment. Sixteen road sites were selected from these suburbs and represented typical industrial, commercial and residential land uses. Build-up pollutants were collected using a wet and dry vacuum collection technique which was specially designed to improve fine particle collection. Roadside soil samples were also collected from each suburb for comparison with the road surface solids. The collected build-up solids samples were separated into four particle size ranges and tested for a range of physical and chemical parameters. The solids build-up on road surfaces contained a high fraction (70%) of particles smaller than 150ìm, which are favourable for heavy metal adsorption. These solids particles predominantly consist of soil derived minerals which included quartz, albite, microcline, muscovite and chlorite. Additionally, a high percentage of amorphous content was also identified in road deposited solids. In comparing the mineralogical data of surrounding soil and road deposited solids, it was found that about 30% of the solids consisted of particles generated from traffic related activities on road surfaces. Significant difference in mineralogical composition was noted in different particle sizes of build-up solids. Fine solids particles (<150ìm) consisted of a clayey matrix and high amorphous content (in the region of 40%) while coarse particles (>150ìm) consisted of a sandy matrix at all study sites, with about 60% quartz content. Due to these differences in mineralogical components, particles larger than and smaller than 150ìm had significant differences in their specific surface area (SSA) and effective cation exchange capacity (ECEC). These parameters, in turn, exert a significant influence on heavy metal adsorption. Consequently, heavy metal content in >150ìm particles was lower than in the case of fine particles. The particle size range <75ìm had the highest heavy metal content, corresponding with its high clay forming minerals, high organic matter and low quartz content which increased the SSA, ECEC and the presence of Fe, Al and Mn oxides. The clay forming minerals, high organic matter and Fe, Al and Mn oxides create distinct groups of charge sites on solids surfaces and exhibit different adsorption mechanisms and bond strength, between heavy metal elements and charge sites. Therefore, the predominance of these factors in different particle sizes leads to different heavy metal adsorption characteristics. Heavy metals show preference for association with clay forming minerals in fine solids particles, whilst in coarse particles heavy metals preferentially associate with organic matter. Although heavy metal adsorption to amorphous material is very low, the heavy metals embedded in traffic related materials have a potential impact on stormwater quality.Adsorption of heavy metals is not confined to an individual type of charge site in solids, whereas specific heavy metal elements show preference for adsorption to several different types of charge sites in solids. This is attributed to the dearth of preferred binding sites and the inability to reach the preferred binding sites due to competition between different heavy metal species. This confirms that heavy metal adsorption is significantly influenced by the physical and chemical parameters of solids that lead to a heterogeneity of surface charge sites. The research study highlighted the importance of removal of solids particles from stormwater runoff before they enter into receiving waters to reduce the potential risk posed by the bioavailability of heavy metals. The bioavailability of heavy metals not only results from the easily mobile fraction bound to the solids particles, but can also occur as a result of the dissolution of other forms of bonds by chemical changes in stormwater or microbial activity. Due to the diversity in the composition of the different particle sizes of solids and the characteristics and amount of charge sites on the particle surfaces, investigations using bulk solids are not adequate to gain an understanding of the heavy metal adsorption processes of solids particles. Therefore, the investigation of different particle size ranges is recommended for enhancing stormwater quality management practices.

Big, bigger, best? The impact of reforms on the not-for-profit sector in Queensland

Organisations within the not-for-profit sector provide services to individuals and groups that government and for-profit organisations cannot or will not consider. The not-for-profit sector has come to be a vibrant and rich agglomeration of services and programs that operate under a myriad of philosophical stances, service orientation, client groupings and operational capacities. In Australia these organisations and services are providing social support and service assistance to many people in the community; often targeting their assistance to the most difficult of clients. Initially, in undertaking this role, the not-for-profit sector received limited sponsorship from government. Over time governments assumed greater responsibility in the form of service grants to particular groups: ‘the worthy poor’. More recently, they have entered into contractual service agreements with the not-for-profit sector, which specify the nature of the outcomes to be achieved and, to a degree, the way in which the services will be provided. A consequence of this growing shift to a more marketised model of service contracting, often offered-up under the label of enhanced collaborative practice, has been increased competitiveness between agencies that had previously worked well together (Keast and Brown, 2006). Another trend emerging from the market approach is the entrance of for-profit providers. These larger organisations have higher levels of organisational capacity with considerable organisational slack to allow them to adopt new service roles. Shaped almost as ‘shadow governments’ they appear to be a strong preference for governments looking for greater accountability of outcomes and an easier way to control the interaction with the conventional not-for-profit sector. The question is will governments’ apparent preference for larger organisational arrangements lead to the demise of the vibrancy of the not-for-profit sector and impact on service provision to those people who fall outside of the remit of the new service providers? To address this issue, this paper uses information gleaned from a state-wide survey of not-for-profit organisations in Queensland, Australia which included organisational size, operational scope, funding arrangements and governance/management approaches. Supplementing this information is qualitative data derived from 17 focus groups and 120 interviews conducted over ten years of study of this sector. The findings contribute to greater understanding of the practice and theory of the future provision of social services.

In their own words: Why teenagers don't use social networking sites

We explored common reasons for non-use of the rapidly growing popularity of social networking sites among a sample of Australian adolescents (N = 69). Transcripts were coded by grouping responses along similar themes for non-use that had been commonly stated by participants. The primary reasons offered by adolescents were: lack of motivation, poor use of time, preference for other forms of communication, preference for engaging in other activities, cybersafety concerns, and a dislike of self-presentation online. The identification of these themes allows for a greater understanding of teenagers' decisions not to engage in the popular medium of communication and points to possible strategies that could be utilised by Web site developers in efforts to appeal to a wider teenage audience.

Improving web database search incorporating users query information

The growing importance and need of data processing for information extraction is vital for Web databases. Due to the sheer size and volume of databases, retrieval of relevant information as needed by users has become a cumbersome process. Information seekers are faced by information overloading - too many result sets are returned for their queries. Moreover, too few or no results are returned if a specific query is asked. This paper proposes a ranking algorithm that gives higher preference to a user’s current search and also utilizes profile information in order to obtain the relevant results for a user’s query.

Creative suburbia : rethinking urban cultural policy – the Australian case

This article considers the question of whether creative workers demonstrate a preference for inner cities or suburbs, drawing upon research findings from the ‘Creative Suburbia’ project undertaken by a team of Australian researchers over 2008–2010 in selected suburban areas of Brisbane and Melbourne. Locating this question in wider debates about the relationship of the suburbs to the city, as well as the development of new suburban forms such as master-planned communities, the article finds that the number of creative industries workers located in the suburbs is significant, and those creative workforce members living and working in suburban areas are generally happy with this experience, locating in the suburbs out of personal choice rather than economic necessity. This runs counter to the received wisdom on creative cities, which emphasize cultural amenity in inner city areas as a primary driver of location decisions for the ‘creative class’. The article draws out some implications of the findings for urban cultural policy, arguing that the focus on developing inner urban cultural amenity has been overplayed, and that more attention should be given to how to better enable distributed knowledge systems through high-speed broadband infrastructure.

Social network analysis of an online dating network

Online social networks can be found everywhere from chatting websites like MSN, blogs such as MySpace to social media such as YouTube and second life. Among them, there is one interesting type of online social networks, online dating network that is growing fast. This paper analyzes an online dating network from social network analysis point of view. Observations are made and results are obtained in order to suggest a better recommendation system for people-to-people networks.

Rational design of serine protease inhibitors

Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.